Correlating the KELIM (CA125 elimination rate constant K) score and the chemo-response score as predictors of chemosensitivity in patients with advanced ovarian carcinoma.

BACKGROUND: The objective of this study is to assess the correlation between the pre-operative CA125 Elimination rate constant K(KELIM) score and the intraoperative chemo-response score (CRS) in patients with advanced high grade serous ovarian cancer(HGSC) treated with neoadjuvant chemotherapy(NACT). METHODS: This is a retrospective cohort study of patients with Stage III-IV HGSC treated with NACT from March 2010 to December 2019 at Princess Margaret Cancer Center, Toronto, Canada. KELIM scores were calculated based on the tool devised by You et al. available online. CRS was assessed using an established 3-tier scoring system. An association analysis was performed to determine if the KELIM score assessed during NACT can predict CRS score at the time of interval cytoreductive surgery(ICS). RESULTS: 172 patients were included in this analysis. Patients with CRS 1-2 had a lower median Platinum Free Interval(PFI) (9.24 vs 13.64 months, p = 0.005), lower median progression free survival(PFS) (14.99 vs 20.29 months, p = 0.003) and lower 5-year overall survival(OS) (63.8% vs 69.7%, p = 0.54) compared to patients with CRS3. Among patients with CRS 1-2(n = 115), 68.7% had KELIM <1, while 56.2% of patients with CRS3 had KELIM ≥1(56.2%), p = 0.0017, suggesting a correlation between the KELIM and CRS scores. Furthermore, patients with KELIM ≥1 and CRS3 had significantly higher PFS compared to other groups(median PFS 28.27 months vs 17.66 months for KELIM ≥1/CRS 1/2; 17.13 months for KELIM <1/CRS 3; and 14.53 months for KELIM <1/CRS 1-2, p = 0.003). CONCLUSION: The biochemical KELIM score correlated with the surgical pathologic CRS score and may predict pathological response to chemotherapy. This information can be utilized to tailor and personalize treatment in patients with advanced ovarian malignancy.

Defining the Longitudinal Risk of CIN 3+ for

OBJECTIVE: To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and

Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study.

OBJECTIVE: Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. METHODS: This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. RESULTS: 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). CONCLUSION: Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.

Using a machine learning algorithm to predict outcome of primary cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: To develop a machine learning (ML) algorithm to predict outcome of primary cytoreductive surgery (PCS) in patients with advanced ovarian cancer (AOC) METHODS: This retrospective cohort study included patients with AOC undergoing PCS between January 2017 and February 2021. Using radiologic criteria, patient factors (age, CA-125, performance status, BRCA) and surgical complexity scores, we trained a random forest model to predict the dichotomous outcome of optimal cytoreduction (<1 cm) and no gross residual (RD = 0 mm) using JMP-Pro 15 (SAS). This model is available at https://ipm-ml.ccm.sickkids.ca. RESULTS: One hundred and fifty-one patients underwent PCS and randomly assigned to train (n = 92), validate (n = 30), or test (n = 29) the model. The median age was 58 (27-83). Patients with suboptimal cytoreduction were more likely to have an Eastern Cooperative Oncology Group 3-4 (11% vs. 0.75%, p = 0.004), lower albumin (38 vs. 41, p = 0.02), and higher CA125 (1126 vs. 388, p = 0.012) than patients with optimal cytoreduction (n = 133). There were no significant differences in age, histology, stage, or BRCA status between groups. The bootstrap random forest model had AUCs of 99.8% (training), 89.6%(validation), and 89.0% (test). The top five contributors were CA125, albumin, diaphragmatic disease, age, and ascites. For RD = 0 mm, the AUCs were 94.4%, 52%, and 84%, respectively. CONCLUSION: Our ML algorithm demonstrated high accuracy in predicting optimal cytoreduction in patients with AOC selected for PCS and may assist decision-making.

Evaluating the use of machine learning in endometrial cancer: a systematic review.

OBJECTIVE: To review the literature on machine learning in endometrial cancer, report the most commonly used algorithms, and compare performance with traditional prediction models. METHODS: This is a systematic review of the literature from January 1985 to March 2021 on the use of machine learning in endometrial cancer. An extensive search of electronic databases was conducted. Four independent reviewers screened studies initially by title then full text. Quality was assessed using the MINORS (Methodological Index for Non-Randomized Studies) criteria. P values were derived using the Pearson's Χ2 test in JMP 15.0. RESULTS: Among 4295 articles screened, 30 studies on machine learning in endometrial cancer were included. The most frequent applications were in patient datasets (33.3%, n=10), pre-operative diagnostics (30%, n=9), genomics (23.3%, n=7), and serum biomarkers (13.3%, n=4). The most commonly used models were neural networks (n=10, 33.3%) and support vector machine (n=6, 20%).The number of publications on machine learning in endometrial cancer increased from 1 in 2010 to 29 in 2021.Eight studies compared machine learning with traditional statistics. Among patient dataset studies, two machine learning models (20%) performed similarly to logistic regression (accuracy: 0.85 vs 0.82, p=0.16). Machine learning algorithms performed similarly to detect endometrial cancer based on MRI (accuracy: 0.87 vs 0.82, p=0.24) while outperforming traditional methods in predicting extra-uterine disease in one serum biomarker study (accuracy: 0.81 vs 0.61). For survival outcomes, one study compared machine learning with Kaplan-Meier and reported no difference in concordance index (83.8% vs 83.1%). CONCLUSION: Although machine learning is an innovative and emerging technology, performance is similar to that of traditional regression models in endometrial cancer. More studies are needed to assess its role in endometrial cancer. PROSPERO REGISTRATION NUMBER: CRD42021269565.

Validation of the Integrated Prediction Model algorithm for outcome of cytoreduction in advanced ovarian cancer.

BACKGROUND: We previously developed the Integrated Prediction Model using a 4-step algorithm of unresectable stage IVB, patient factors, surgical resectability, and surgical complexity to predict outcome of <1 cm cytoreduction in advanced epithelial ovarian cancer, and triaged patients to neoadjuvant chemotherapy or primary cytoreductive surgery. OBJECTIVE: To validate the Integrated Prediction Model on a retrospective cohort of patients. METHODS: A retrospective cohort study of 107 patients with advanced ovarian cancer treated between January 2017 and September 2018 was carried out. The above mentioned 4-step algorithm determined cut-off points using the Youden Index. This validation study reports sensitivity, specificity, negative and positive predictive value on an external cohort. RESULTS: Among 107 patients, 61 had primary surgery and 46 had neoadjuvant chemotherapy. Compared with primary surgery, patients treated with neoadjuvant chemotherapy were significantly older (63.5 vs 61, p=0.037), more likely to have stage IV disease (52% vs 18%, p<0.001), Eastern Cooperative Oncology Group (ECOG) score >1 (30% vs 11%, 0.045), lower pre-operative albumin (37 vs 40, p<0.001), and higher CA-125 (970 vs 227.5, p<0.001). They also had higher patient factors (2 vs 0, p=0.013), surgical resectability (4 vs 1, p<0.001), and anticipated surgical complexity (8 vs 5, p<0.001). There was no significant difference in outcome of cytoreduction (<1 cm residual disease: 85% for primary surgery vs 87% interval surgery, p=0.12)In this validation cohort, triaging patients with patient factors ≤2, surgical resectability score ≤5, and surgical complexity score ≤9 to primary surgery had a sensitivity of 91% for optimal cytoreduction <1 cm and a specificity of 81%. The positive predictive value, negative predictive value, and accuracy were 83%, 90%, and 86%, respectively. Application of the Integrated Prediction Model would have prevented five patients from receiving suboptimal cytoreduction and triaged them to neoadjuvant chemotherapy. CONCLUSIONS: We validated the proposal that a triage algorithm integrating patient factors, surgical complexity, and surgical resectability in advanced ovarian cancer had high sensitivity and specificity to predict optimal cytoreduction <1 cm.

Validation of the KELIM score as a predictor of response to neoadjuvant treatment in patients with advanced high grade serous ovarian cancer.

OBJECTIVE: The objective of this study is to externally validate the KELIM (rate of elimination of CA-125 elimation) score in patients with high grade serous ovarian cancer(HGSC)undergoing NACT and determine its relation to outcome of cytoreduction, platinum sensitivity, progression free(PFS) and overall survival(OS). METHODS: This is a retrospective cohort study of patients with Stage III-IV HGSC diagnosed between January 1, 2010 and December 31, 2019 and treated with NACT. KELIM score was calculated using at least 3 CA-125 values within the first 100 days of chemotherapy. Demographic parameters were collected and Kaplan Meier survival analyses were performed for PFS and OS. This study was approved by local ethics board. RESULTS: 217 patients met inclusion criteria. Median follow-up was 28.93 months(range 2.86-135.06). There was no significant difference in stage, functional status, cytoreductive outcome or BRCA status(germline or somatic) between patients with a KELIM ≥ 1 and <1. Patients with a KELIM<1 had a lower median PFS (13.58 vs 19.69, p < 0.001), median platinum free interval(PFI) (7.66 vs 13.64, p < 0.001) and 5-year OS (57% vs 72%, p = 0.0140) compared to patients with KELIM≥1 . After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase(parp)-inhibitor use, and BRCA status, patients with KELIM<1 had a high risk of disease progression(HR = 1.57 (95% CI 1.08-2.28) and death(HR = 1.99 (95% CI 1.01-3.95) compared to KELIM≥1. BRCA status was independently associated to an increase on KELIM score (OR = 1.917, 95% CI 1.046-3.512, p = 0.035). CONCLUSION: Patients with advanced HGSC undergoing NACT with a KELIM <1 were more likely to have platinum-resistant disease, worse PFS and worse OS when compared to patients with KELIM≥1. The KELIM score can be a helpful tool to predict chemo-response and aid in treatment decision making.

Integrated prediction model of patient factors, resectability scores and surgical complexity to predict cytoreductive outcome and guide treatment plan in advanced ovarian cancer.

OBJECTIVE: To report performance of an integrated predictive model (IPM) algorithm based on patient factors, surgical resectability and surgical complexity to predict outcome of primary cytoreductive surgery (PCS) and guide treatment plan in patients with advanced epithelial ovarian cancer (AEOC). METHODS: Patients with AEOC between October 2018 and October 2020 were enrolled into a dedicated AEOC program and decision for PCS or neoadjuvant chemotherapy (NACT) was based on multidisciplinary consensus. Data of unresectable stage IVb, patient factors (PF), surgical resectability scores (SRS) and surgical complexity scores (SCS) was prospectively documented. An integrated prediction model (IPM) was developed to predict outcome of optimal (RD < 1 cm) cytoreduction. Retrospective analysis was performed to assess the performance of the IPM. Cut-offs were selected using the Youden Index. RESULTS: Of 185 eligible patients, 81 underwent PCS and 104 were treated with NACT. Patients undergoing PCS had significantly lower median PF (0 vs 2, p < 0.01), SRS (2 vs 4, p < 0.01) and pre-operative SCS (6 vs 8.5, p = 0.01) compared to NACT. In patients undergoing PCS, 88% had optimal cytoreduction and 34.5% had grade 3-4 post-operative complications. A model triaging patients with unresectable Stage IVb, PF > 2, SRS > 5 and SCS > 9 to NACT had 85% sensitivity, 75% specificity and 85% accuracy for outcome of optimal cytoreduction. Our model would have improved triage of 3/10 sub-optimally cytoreduced patients to NACT. For outcome of no-gross residual disease (RD = 0 mm) using the same cut-offs sensitivity and specificity were 85% and 76% respectively. CONCLUSION: The 4-step IPM algorithm had high sensitivity and specificity for optimal cytoreduction with acceptable morbidity without delay to adjuvant therapy. This algorithm may be used to triage patients to PCS or NACT once it is further validated.

Comparison of outcomes between abdominal, minimally invasive and combined vaginal-laparoscopic hysterectomy in patients with stage IAI/IA2 cervical cancer: 4C (Canadian Cervical Cancer Collaborative) study.

OBJECTIVE: Although minimally invasive hysterectomy (MIS-H) has been associated with worse survival compared to abdominal hysterectomy (AH) for cervical cancer, only 8% of patients in the LACC trial had microinvasive disease (Stage IA1/IA2). We sought to determine differences in outcome among patients undergoing MIS-H, AH or combined vaginal-laparoscopic hysterectomy (CVLH) for microinvasive cervical cancer. METHODS: A retrospective cohort study of all patients undergoing hysterectomy (radical and non radical) for FIGO 2018, microinvasive cervical cancer across 10 Canadian centers between 2007 and 2019 was performed. Recurrence free survival (RFS) was estimated using Kaplan Meier Survival analysis. Chi-square and log-rank tests were used to compare outcomes. RESULTS: 423 patients with microinvasive cervical cancer were included; 259 (61.2%) Stage IA1 (22/8.5% with LVSI) and 164(38.8%) IA2. The median age was 44 years (range 24-81). The most frequent histology was squamous (59.4%). Surgical approach was: 50.1% MIS-H (robotic or laparoscopic), 35.0% AH and 14.9% CVLH. Overall, 70.9% underwent radical hysterectomy and 76.5% had pelvic lymph node assessment. There were 16 recurrences (MIS-H:4, AH:9, CVLH: 3). No significant difference in 5-year RFS was found (96.7% MIS-H, 93.7% AH, 90.0% CVLH, p = 0.34). In a sub-analysis of patients with IA1 LVSI+/IA2(n = 186), survival results were similar. Further, there was no significant difference in peri-operative complications (p = 0.19). Patients undergoing MIS-H had a shorter median length of stay(0 days vs 3 (AH) vs. 1.5 (CVLH), p < 0.001), but had more ER visits (16.0% vs 3.6% (AH), 3.5% (CVLH), p = 0.036). CONCLUSION: In this cohort, including only patients with microinvasive cervical cancer, no difference in recurrence was found by surgical approach. This may be due to the low rate of recurrence making differences hard to detect or due to a true lack of difference. Hence, this patient population may benefit from MIS without compromising oncologic outcomes.

Treatment outcomes and predictive factors in patients ≥70 years old with advanced ovarian cancer.

OBJECTIVE: To evaluate treatment outcomes, survival, and predictive factors in patients ≥70 with advanced epithelial ovarian cancer (AEOC). METHODS: A retrospective single institution cohort study of women ≥70 with Stage III-IV AEOC between 2010 and 2018. Patients had either primary cytoreductive surgery (PCS), neoadjuvant chemotherapy (NACT) with interval cytoreductive surgery (ICS), chemotherapy alone, or no treatment. Demographics, surgical outcome, complications, and survival outcome were compared between groups. RESULTS: Among 248 patients, 69 (27.7%) underwent PCS, 99 (39.9%) had ICS, 56 (22.5%) had chemotherapy alone. Twenty-four (9.6%) remained untreated. Optimal cytoreduction (≤1 cm) was achieved in 72.4% of PCS and 77.8% of NACT/ICS (p = 0.34), without difference in grade ≥3 postoperative complications (15.9% vs. 9.1%, p = 0.37). Progression-free survival (PFS) was 23.5 months in PCS and 15.0 months in ICS patients (hazard ratio [HR]: 1.4, p = 0.041). Patients in the surgical arms, PCS or ICS, had better 2-year overall survival (OS) compared to chemotherapy alone (79%, 68%, 41%, respectively, HR: 3.58, p < 0.001). In a subgroup analysis, patients ≥80 had improved 2-year OS when treated with NACT compared to PCS (82% vs. 57%) and a trend toward improved PFS. Age, stage, and CA-125 were determinants of undergoing PCS. CONCLUSION: In patients ≥70 with AEOC, surgery should not be deferred based on age alone. Fit, well selected patients ≥70 can benefit from PCS, while patients ≥80 might benefit from NACT over PCS.

Predicting recurrence and recurrence-free survival in high-grade endometrial cancer using machine learning.

OBJECTIVE: To develop machine-learning models to predict recurrence and time-to-recurrence in high-grade endometrial cancer (HGEC) following surgery and tailored adjuvant treatment. METHODS: Data were retrospectively collected across eight Canadian centers including 1237 patients. Four models were trained to predict recurrence: random forests, boosted trees, and two neural networks. Receiver operating characteristic curves were used to select the best model based on the highest area under the curve (AUC). For time to recurrence, we compared random forests and Least Absolute Shrinkage and Selection Operator (LASSO) model to Cox proportional hazards. RESULTS: The random forest was the best model to predict recurrence in HGEC; the AUCs were 85.2%, 74.1%, and 71.8% in the training, validation, and test sets, respectively. The top five predictors were: stage, uterus height, specimen weight, adjuvant chemotherapy, and preoperative histology. Performance increased to 77% and 80% when stratified by Stage III and IV, respectively. For time to recurrence, there was no difference between the LASSO and Cox proportional hazards models (c-index 71%). The random forest had a c-index of 60.5%. CONCLUSIONS: A bootstrap random forest model may be a more accurate technique to predict recurrence in HGEC using multiple clinicopathologic factors. For time to recurrence, machine-learning methods performed similarly to the Cox proportional hazards model.

Gynecologic oncology treatment modifications or delays in response to the COVID-19 pandemic in a publicly funded versus privately funded North American tertiary cancer center.

OBJECTIVE: To compare gynecologic oncology surgical treatment modifications and delays during the first wave of the COVID-19 pandemic between a publicly funded Canadian versus a privately funded American cancer center. METHODS: This is a retrospective cohort study of all planned gynecologic oncology surgeries at University Health Network (UHN) in Toronto, Canada and Brigham and Women's Hospital (BWH) in Boston, USA, between March 22,020 and July 302,020. Surgical treatment delays and modifications at both centers were compared to standard recommendations. Multivariable logistic regression was performed to adjust for confounders. RESULTS: A total of 450 surgical gynecologic oncology patients were included; 215 at UHN and 235 at BWH. There was a significant difference in median time from decision-to-treat to treatment (23 vs 15 days, p < 0.01) between UHN and BWH and a significant difference in treatment delays (32.56% vs 18.29%; p < 0.01) and modifications (8.37% vs 0.85%; p < 0.01), respectively. On multivariable analysis adjusting for age, race, treatment site and surgical priority status, treatment at UHN was an independent predictor of treatment modification (OR = 9.43,95% CI 1.81-49.05, p < 0.01). Treatment delays were higher at UHN (OR = 1.96,95% CI 1.14-3.36 p = 0.03) and for uterine disease (OR = 2.43, 95% CI 1.11-5.33, p = 0.03). CONCLUSION: During the first wave of COVID-19 pandemic, gynecologic oncology patients treated at a publicly funded Canadian center were 9.43 times more likely to have a surgical treatment modification and 1.96 times more likely to have a surgical delay compared to an equal volume privately funded center in the United States.

BRCA testing in women with high-grade serous ovarian cancer: gynecologic oncologist-initiated testing compared with genetics referral.

OBJECTIVE: Up to 15% of patients with high-grade serous ovarian, tubal, or peritoneal carcinoma harbor a mutation in BRCA genes. Early notion of mutation status may facilitate counseling, predict prognosis, and increase access to Parp-inhibitors. The aim of this study was to examine the rate of germline genetic testing in a retrospective cohort of women with high-grade serous ovarian, tubal, or peritoneal carcinoma to determine if a new pilot project of gynecologic oncologist-initiated genetic testing improved the rate of testing, after 1 year of implementation. METHODS: Gynecologic oncology-initiated genetic testing was implemented at a single university hospital center with input and collaboration from gynecological oncologists, nurses, and genetic counselors. All patients diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma after August 2017 were offered gynecologic oncologist- initiated genetic testing for a panel of 13 hereditary breast and ovarian cancer susceptibility genes. Data from this group was then compared with a historic cohort of patients who received traditional genetic counseling between January 2014 and August 2017 (control group). Patients that had genetic testing through a clinical trial were excluded. The primary outcome was the uptake of genetic testing in both groups. Secondary outcomes included difference in time from diagnosis to genetic result between both cohorts. Data was analyzed using SPSS 25.0 and medians (ranges) were reported. RESULTS: A total of 152 women with high-grade serous ovarian, tubal, or peritoneal carcinoma were included in this study. Between January 2014 to July 2017 there were 108 patients with high-grade serous ovarian, tubal, or peritoneal carcinoma, among which 50.9% (n=54) underwent genetic testing following referral to genetics. The prevalence of BRCA pathogenic variants was 25.9% (14/54): 9.2% (5/54) in BRCA1 and 16.7% (9/54) in BRCA2. The median time from diagnosis to genetics referral was 53 days (range; 3-751), and median time from diagnosis to test result disclosure was 186 days (range; 15-938). After 1 year of implementation of the gynecologic oncologist-initiated genetic testing model, among 44 women diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma, 86.2% underwent genetic testing. The median time from diagnosis to result disclosure decreased to 58 days, representing a reduction of 128 days, or 4.27 months (P<0.001). Reasons for non-testing included refusal, death, and follow-up at another hospital. The prevalence of germline BRCA1/2 pathogenic variants was 21% (8/38). CONCLUSION: Gynecologic oncologist-initiated genetic testing at the time of high-grade serous ovarian, tubal, or peritoneal carcinoma diagnosis leads to increased uptake and decreased delays in testing compared with referral for traditional genetic counseling.

CA-125 reduction during neoadjuvant chemotherapy is associated with success of cytoreductive surgery and outcome of patients with advanced high-grade ovarian cancer.

INTRODUCTION: The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome. MATERIAL AND METHODS: This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population. RESULTS: In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05). CONCLUSIONS: Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer.

Similar Overall Survival Using Neoadjuvant Chemotherapy or Primary Debulking Surgery in Patients Aged Over 75 Years with High-Grade Ovarian Cancer.

OBJECTIVE: To perform a hypothesis-generating evaluation of patient outcomes following neoadjuvant chemotherapy (NACT) compared with those following primary debulking surgery (PDS) in patients over age 75 with high-grade ovarian cancer. METHODS: This was a retrospective cohort study of consecutive patients aged 75 years and older, with high-grade ovarian cancer. Data were analyzed in SPSS 25.0 using descriptive statistics to characterize groups based on primary treatment modality, Kaplan-Meier survival curves to estimate overall and progression-free survival, and Cox proportional hazards to analyze confounders. RESULTS: Of 429 patients with stages III and IV high-grade ovarian cancer (endometrioid and serous), 71 were aged older than 75 years and met our criteria for inclusion; 58 were treated with NACT while 13 underwent primary debulking. Sixteen patients did not undergo interval debulking following NACT. There were no significant differences in demographic characteristics between the groups. Following NACT, more patients were completely debulked-36.2% versus 21% (P = 0.000)-and had a shorter length of stay (5 vs. 7 d; P = 0.018). Overall survival was similar between the NACT and PDS groups (58.7 vs. 59.7 mo; LR -0.836; P = 0.361) despite lower progression-free survival in the NACT group (25.9 vs. 47.1 mo; P = 0.042; LR 4.31). Both progression-free and overall survival were significantly higher when patients undergoing NACT achieved complete debulking (21.7 and 102.3 mo, respectively) compared with suboptimal debulking (12.03 and 14.2 mo, respectively). CONCLUSION: In this select group older patients with stage III and IV high-grade ovarian cancers, neoadjuvant chemotherapy may be considered without compromising outcomes and contributes to complete debulking.

Robotic Radical Hysterectomy for Cervical Cancer: A Population-Based Study of Adoption and Immediate Postoperative Outcomes in the United States.

STUDY OBJECTIVE: To compare the use of robotic radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) in the United States, with secondary outcomes of perioperative complications, hospital length of stay (LOS), immediate postoperative mortality, cost and a subanalysis compared with laparoscopic radical hysterectomy (LRH). DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Data from the National Inpatient Sample (NIS), a government-funded database of hospitalization in the United States. PATIENTS AND INTERVENTIONS: All women with cervical cancer undergoing RH between 2008 and 2015 in the United States and included in the NIS database. MEASUREMENTS AND MAIN RESULTS: Trends in surgical modality, baseline characteristics, LOS, perioperative outcomes, mortality, and hospital charges were compared between RRH and ARH. Regression models were adjusted for baseline characteristics. Among 41,317 women with cervical cancer, 3563 underwent RH, including 21.0% with a robotic procedure, 6.5% with a laparoscopic procedure, and 72.5% with open surgery. The annual rates of ARH declined significantly over the study period, whereas those of RRH increased. Baseline characteristics were comparable between the RRH and ARH groups. Compared with the ARH group, women undergoing RRH had a lower rate of cumulative postoperative complications (18.16% vs 21.21%; odds ratio [OR], 0.81; 95% confidence interval [CI], 0.6-1.0; p = .05), including lower rates of wound infection (0.27% vs 1.82%; OR, 0.14; 95% CI, 0.03-0.6; p < .01), sepsis (0.27% vs 1.20%; OR, 0.22; 95% CI, 0.05-0.9; p = .03), fever (1.87% vs 4.06%; OR, 0.44, 95% CI, 0.3-0.8; p < .01), and ileus (2.8% vs 9.13%; OR, 0.28; 95% CI, 0.12-0.4; p < .01). The LOS was significantly shorter in the RRH group (median, 2 days vs 4 days; p < .01). The total median hospitalization charge was $47,218 for the RRH group, compared with $38,877 for the ARH group (p < .01). CONCLUSION: RRH is being increasingly performed in the United States and is associated with shorter LOS and less postoperative morbidity; however, long-term oncologic outcomes require additional attention.

Clinical significance of isolated tumor cells and micrometastasis in low-grade, stage I endometrial cancer.

INTRODUCTION: Ultrastaging in endometrial cancer (EC) led to increased detection of isolated tumor cells (ITC, ≤0.2 mm) and micrometastases (MM, 0.2-2 mm), with unclear effect on prognosis. Our aim was to characterize the impact of ITC and MM on the outcome of these patients. METHODS: Grade 1 to 2 stage I endometrioid EC patients with nodal ITC (n = 11) or MM (n = 12) between 2012 and 2018 were retrospectively compared to a matched group of lymph node negative (n = 18) patients based on age, body mass index, grade, myometrial invasion, and lymphovascular space invasion (LVI) status using propensity score analysis (1:1). Mann-Whitney U tests were performed on continuous variables and χ2 tests on categorical variables. Progression-free survival (PFS) was the main endpoint. RESULTS: All MM and 81% of ITC had LVI. More ITC/MM patients received RT and chemotherapy (91.7% vs 18.4%; 70.8% vs 4.5%, respectively; P < 0.01) without significant difference in treatment-related toxicities (25% vs 27.3% grade 1%-2% and 20.8% vs 9.1% grade 2-3; P = 0.538) or PFS (29.2 vs 25 months; P = 0.828). Two distant recurrences occurred in MM patients after 2.5 years; one lung and one para-aortic lymph node. CONCLUSION: With adjuvant treatment, ITC/MM in otherwise well-differentiated stage I endometrial cancer have similar outcomes to matched LN- patients.

Impact of an HPV Education and Vaccination Campaign among Canadian University Students.

BACKGROUND: Uptake of HPV vaccination among university students remains low despite risky sexual practices and increased prevalence of high-risk HPV genotypes. The study objective was to determine the level of knowledge related to HPV and cervical cancer among university students and to subsequently develop a targeted education and vaccination campaign to increase uptake. METHODS: Phase I was a pilot project in which participants were recruited as part of Cervical Cancer Awareness Week 2015 at two universities, one site immediately offering vaccination and the other not. A self-administered questionnaire was used to collect demographic information from participants and evaluate their baseline knowledge related to HPV and the risks of cervical cancer, in addition to determining barriers to vaccination and future willingness to be vaccinated. Data was compiled and analyzed using descriptive statistics of means and percentages. In phase II, which followed 1 year after, a targeted education and vaccination campaign was designed based on lessons learned from phase I, and vaccination uptake was reevaluated after 1 year. RESULTS: In phase I, 56 participants responded to a questionnaire related to HPV knowledge and cervical cancer. Among these, 29 students were vaccinated in a 2-day resident-run clinic. Overall, 63% felt they were not at risk of cervical cancer, though 88% knew HPV was the cause of cervical cancer. The three barriers identified to previous vaccination were lack of access to a doctor or a nurse (25%), financial reasons (25%), and low self-perceived risk (7%). There was a 50% three-dose completion rate in phase I. Based on this information, the education campaign in phase II was expanded in the subsequent year through social media, email communication, information booths, and individual solicitation. A total of 151 students were approached for individual solicitation and education. Among these, 64 students were vaccinated on site, including five men. Most importantly, there were 18 walk-ins resulting directly from the education initiatives and person-to-person solicitation. Subsequently, in 2016, 502 students were vaccinated at the McGill student health clinic and 455 at Concordia University. CONCLUSION: HPV vaccination rates in university students are readily increased through educational campaigns, of which person-to-person solicitation proved to be the most fruitful in this study. Identifying barriers to vaccination can guide future initiatives to maximize impact.

Incidence and causes of maternal mortality in the USA.

AIM: To characterize the most common causes and risk factors of maternal mortality in the USA and observe trends over the past 9 years. METHODS: We carried out a population-based retrospective cohort study using data from the Health Care Cost and Utilization Project, Nationwide Inpatient Sample. Women who were pregnant between 2003 and 2011 were identified. Baseline characteristics of pregnant women who died and those who lived were measured. ICD-9 codes for each cause of death were examined by up to three independent reviewers. Causes of death were categorized into the nine most common subgroups and trends were examined by tertiles of the period 2003-2011. RESULTS: During this 9-year period, there were approximately 7 million births and 1102 maternal deaths, for an overall incidence of 14.2 per 100 000 births. Primary causes of maternal death included sepsis (20.6%), cardiac disease (17.8%), hemorrhage (16.2%), venous thromboembolism (15.2%), and hypertensive disorders (9.4%). During the study period, there was a significant decrease in the frequency of sepsis from 33.2% to 10.0% and a non-significant decrease in venous thromboembolism from 19.1% to 12.9%. There were increases noted in all other groups, notably in terms of hemorrhage from 8.2% to 22.0% and hypertensive disorders from 2.1% to 16.4%. CONCLUSION: Maternal mortality remains a rare event. Although sepsis was the overall predominant cause of mortality during the study period, frequency declined over time and it was surpassed by hemorrhage and hypertensive disorders as the leading causes of maternal mortality.

Early experience with robotic pancreatic surgery in a Canadian institution.

BACKGROUND: Pancreatic resections have traditionally been associated with substantial morbidity and mortality. The robotic platform is believed to improve technical aspects of the procedure while offering minimally invasive benefits. We sought to determine the safety and feasibility of the first robotic pancreaticoduodenectomies performed at our institution. METHODS: We retrospectively reviewed data on all patients who underwent robotic-assisted pancreaticoduodenectomy (RAPD) between July 2010 and June 2014 and compared them to outcomes of patients undergoing hybrid laparoscopic pancreaticoduodenectomies (HLAPD) during the same time period. RESULTS: Fifteen patients were scheduled for RAPD; 2 were converted to an open approach and 1 to a mini-laparotomy during the laparoscopic portion of the procedure. Patients who had RAPD (n = 12) had a median duration of surgery of 596.6 (range 509-799) minutes, estimated blood loss of 275 (range 50-1000) mL and median length of stay of 7.5 (range 5-57) days. Mean total opioid use up to postoperative day 7 was 142.599 ± 68.2 versus 176.9 ± 112.7 mg equivalents of intravenous morphine for RAPD and HLAPD, respectively. There was no significant difference between RAPD and HLAPD in any parameters, highlighting the safety and feasibility of a step-wise minimally invasive learning platform. Most patients in the RAPD group had malignant pathology (88.2%). Oncologic outcomes were maintained with no significant difference in ability to resect lymph nodes or achieve negative margins. There were 4 (28.5%) Clavien I-II complications and 3 (29.4%) Clavien III- IV complications, 2 of which required readmission. There were no reported deaths at 90 days. Complication, pancreatic leak and mortality rates did not differ significantly from our laparoscopic experience. CONCLUSION: Outcomes of RAPD and HLAPD were comparable at our centre, even during the early stages of our learning curve. These results also highlight the safety, feasibility and patient benefits of a step-wise transition from open to hybrid to fully robotic pancreaticoduodenectomies in a high-volume academic centre.

CONTEXTE: L'ablation du pancréas a de tout temps été associée à une morbidité et une mortalité importantes. Le recours à une plateforme assistée par robot devrait vraisemblablement améliorer les aspects techniques de l'intervention et offrir en même temps les avantages d'une intervention minimalement effractive. Nous avons voulu déterminer l'innocuité et la faisabilité des premières pancréatoduodénectomies assistées par robot effectuées dans notre établissement. MÉTHODES: Nous avons passé en revue de manière rétrospective les données concernant tous les patients ayant subi une pancréatoduodénectomie assistée par robot (PDAR) entre juillet 2010 et juin 2014 et nous les avons comparées aux résultats enregistrés chez les patients ayant subi une pancréatoduodénectomie laparoscopique hybride (PDLH) au cours de la même période. RÉSULTATS: Quinze patients ont été pressentis pour une PDAR; 2 ont plutôt subi une intervention ouverte et 1 a subi une mini-laparotomie durant la portion laparoscopique de l'intervention. Chez les patients soumis à la PDAR (n = 12), la durée médiane de la chirurgie a été de 596,6 (plage de 509 à 799) minutes, les pertes sanguines estimées ont été de 275 (plage de 50 à 1000) mL et la durée médiane du séjour hospitalier a été de 7,5 (plage de 5 à 57) jours. L'utilisation totale moyenne d'opioïdes jusqu'au septième jour postopératoire a été de 142,599 ± 68,2 mg équivalents de morphine intraveineuse contre 176,9 ± 112,7 pour la PDAR et la PDLH, respectivement. On n'a noté aucune différence significative entre la PDAR et la PDLH au plan des paramètres, ce qui souligne l'innocuité et la faisabilité d'une plateforme d'apprentissage séquentielle minimalement effractive. La plupart des patients du groupe soumis à la PDAR étaient atteints d'un cancer (88,2 %). Les paramètres oncologiques se sont maintenus, sans différence significative quant à la capacité de réséquer les ganglions lymphatiques ou d'obtenir des marges négatives. On a dénombré 4 (28,5 %) complications de stade I­II et 3 (29,4 %) de stade III­IV selon la classification de Clavien; 2 de ces dernières ont nécessité une réadmission. On n'a déploré aucun décès à 90 jours. Les taux de complications, de fuite pancréatique et de mortalité n'ont pas différé significativement par rapport à nos interventions laparoscopiques. CONCLUSION: Les résultats de la PDAR et de la PDLH ont été comparables dans notre établissement, même aux premières étapes de notre courbe d'apprentissage. De tels résultats soulignent l'innocuité, la faisabilité et les bienfaits pour les patients d'une transition graduelle des pancréatoduodénectomies ouvertes, hybrides puis entièrement assistées par robot dans un centre universitaire traitant de forts volumes de patients.